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SUMMARY UMMARY UMMARY
n 2015, an estimated 231, 840 new cases of invasive breast cancer would be diagnosed among women, as well as an estimated 60, 290 additional cases of in situ breast cancer. In 2015, approximately 40, 290 women were expected to die from breast cancer. Only lung cancer accounts for more cancer deaths in women. In 2015, about 2, 350 men was diagnosed with breast cancer and 440 men would die from the disease.
The development of breast cancer is associated with numerous risk factors, including genetic, environmental and hormonal influences, yet 75% of women with this cancer have no readily identifiable risk factors.
Most of the breast malignancies are adenocarcinomas, which constitute more than 95% of breast cancers. Invasive ductal carcinoma (IDC) is the most common phenotypic subtype of all Breast cancers comprising nearly 80% of them. Breast cancer is mainly categorized into in situ carcinoma (noninvasive) and invasive breast carcinoma.
Historically, breast cancer classification systems were based on histopathological assessment. Recently, there has been a great progress in molecular analysis which allowed understanding of breast cancer biology and its classification. Expression of estrogen receptor (ER), progesterone receptor (PR) and over-expression and/ or amplification of the human
epidermal growth factor receptor 2 (HER2) have been included to refine classification for predicting prognosis and potential response to treatment.
The diagnosis of breast cancer is based on clinical examination combined with imaging, and confirmed by pathological assessment.
Clinical staging includes physical examination, which includes careful inspection and palpation of the skin, mammary gland, and regional lymph nodes, as well as imaging, and pathologic examination of the breast tissue to establish the diagnosis of breast carcinoma. Imaging findings should include the size of the primary tumor, presence of chest wall invasion, and the presence or absence of regional or distant metastases.
Locally advanced breast cancer (LABC) was initially defined as a heterogeneous group of tumors deemed inoperable either by size or by location. More recently, the definition has evolved to include tumors larger than 5 cm (T3N0 or T3N1) or the presence of bulky metastatic lymph nodes on physical exam (stage iib–iiic). Although the natural history of labc often varies depending on biologic subtype [for example, hormone and her2 (human epidermal growth factor receptor 2) status], staging criteria are still based on the anatomic features of tumor size and lymph node involvement.
Traditionally, preoperative (“neoadjuvant”) systemic therapy has been used to downstage tumors in the hope of making inoperable disease operable. In recent years, neoadjuvant therapy has increasingly been used in patients with operable disease. The objectives in this setting include improving surgical choice (that is, the ability to choose breast-conserving therapy) and allowing for an assessment of the in vivo response to systemic treatment. A number of clinical studies have even made use of the in vivo response to conduct sequential tissue biopsies and assess a range of biomarkers of resistance and sensitivity to neoadjuvant treatment. It had been hoped that earlier introduction of systemic therapy in the neoadjuvant setting would be associated with a survival advantage over traditional postoperative adjuvant therapy. Sadly, however, such an advantage has not been seen in most studies, but its potential remains an area of great interest for tumors of specific molecular subtypes such as her2-positive or triple-negative.
A review of the literature revealed 32 relevant studies that investigated the concordance of the hormone receptors (ER and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the hormone receptor status was reported in four out of eight studies in 8-33% of the patients. About half of the studies that tested the ER and PR receptor status separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies that concluded that ER and/or PR receptor remained
stable after NAC were performed with evidently lower number of patients compared to studies that reported a change. Good concordance of the HER2 amplification tested with FISH was reported, although the HER2 expression measured with immunohistochemistry was more discordant. A switch to a negative HER2 receptor in up to 43% of the patients was reported when NAC was combined with trastuzumab.
The timing of the surgical resection of a breast cancer relative to the chemotherapy regimen needed to minimize metastatic recurrence depends upon the disease presentation and input from the patient. A reasonable, clear indication for neoadjuvant chemotherapy is the need to reduce tumor size in an effort to provide breast conservation as an option. A typical patient for this would be a woman with small to medium breast size with a relatively large cancer who would prefer breast conservation as an option. This down staging of tumor size to avoid a mastectomy has been well documented with long-term loco-regional recurrence and survival rates being similar to traditional adjuvant chemotherapy treatment